Remission Criteria For Schizophrenia Research Articles

SU114. Switching to Clozapine Treatment in Patients With Schizophrenia: The Clinical Course, Remission, and Augmentation of Treatment After the Switch

Background: This study aims to compare clinical features of schizophrenia patients before and after clozapine initiation and to investigate the clinical course of illness, clinical features, remission state, and augmentation methods under clozapine treatment. Methods: A total of 122 consecutive outpatients diagnosed with DSM-IV criteria for schizophrenia and receiving clozapine treatment were included. Patients were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders, Positive and Negative Syndrome Scale, Clinical Global Impression Scale, Global Assessment of Functioning, Calgary Depression Scale for Schizophrenia, Panic Agoraphobia Scale, Yale-Brown Obsessive Compulsive Scale, and the World Health Organization Disability Assessment Schedule-2.0 to determine the severity of psychopathology and comorbid symptoms, as well as the level of functioning and disability. The remission state of the patients was assessed utilizing the Schizophrenia Working Group’s remission criteria for schizophrenia. Results: The number of psychotic relapses, hospitalizations, and suicide attempts along with alcohol-drug misuse rates declined after the initiation of clozapine. The study group consisted of schizophrenia patients using clozapine for a mean period of 9 years, and 44.5% of these patients were found to be in a symptomatic remission state. No relationship was shown between remission state and clozapine dose/plasma levels. Education level was found to be higher, work status better, and comorbid symptom severity lower in remitted patients. There was no difference between remitted and not remitted patients in terms of the duration of clozapine use and age at disease onset. Education level, positive and negative symptom severity predicted achievement of remission on clozapine. The augmentation strategies were examined in patients showing partial response to clozapine, and combined antipsychotic drug use was found to be the most prevalent method utilized. Patients on augmentation treatment were on higher daily clozapine doses and their remission rates were lower. In addition, the severity of psychopathology related with schizophrenia and comorbid symptoms, the level of functioning and disability were worse in this particular patient group. History of antipsychotic combination use prior to clozapine was found to predict the future use of clozapine augmentation. Conclusion: Shortening the duration of switch to clozapine and avoiding antipsychotic combinations prior to clozapine use should both be considered as important goals in the management of treatment resistant schizophrenia.

Proposed criteria for schizophrenia remission.

Proposed criteria for schizophrenia remission Bandar AlAqeel Department of Psychiatry, University of Toronto, Toronto, ON, CanadaI read with interest the article recently published in Neuropsychiatric Disease and Treatment, titled, "Design and validation of standardized clinical and functional remission criteria in schizophrenia" by Mosolov et al.1 I have a few comments here about the design and reporting of their study. View original paper by Mosolov and colleagues.

Design and validation of standardized clinical and functional remission criteria in schizophrenia.

BackgroundInternational Remission Criteria (IRC) for schizophrenia were developed recently by a group of internationally known experts. The IRC detect only 10%–30% of cases and do not cover the diversity of forms and social functioning. Our aim was to design a more applicable tool and validate its use – the Standardized Clinical and Functional Remission Criteria (SCFRC).MethodsWe used a 6-month follow-up study of 203 outpatients from two Moscow centers and another further sample of stable patients from a 1-year controlled trial of atypical versus typical medication. Diagnosis was confirmed by International Classification of Diseases Version 10 (ICD10) criteria and the Mini-International Neuropsychiatric Interview (MINI). Patients were assessed by the Positive and Negative Syndrome Scale, including intensity threshold, and further classified using the Russian domestic remission criteria and the level of social and personal functioning, according to the Personal and Social Performance Scale (PSP). The SCFRC were formulated and were validated by a data reanalysis on the first population sample and on a second independent sample (104 patients) and in an open-label prospective randomized 12-month comparative study of risperidone long-acting injectable (RLAI) versus olanzapine.ResultsOnly 64 of the 203 outpatients (31.5%) initially met the IRC, and 53 patients (26.1%) met the IRC after 6 months, without a change in treatment. Patients who were in remission had episodic and progressive deficit (39.6%), or remittent (15%) paranoid schizophrenia, or schizoaffective disorder (17%). In addition, 105 patients of 139 (51.7%), who did not meet symptomatic IRC, remained stable within the period. Reanalysis of data revealed that 65.5% of the patients met the SCFRC. In the controlled trial, 70% of patients in the RLAI group met the SCFRC and only 19% the IRC. In the routine treatment group, 55.9% met the SCFRC and only 5.7% the IRC. Results of the further independent sample demonstrated that 35% met the IRC, 65% the SCFRC, and 56% of patients met both the symptomatic and functional criteria. In the controlled trial of RLAI and olanzapine, 40% and 35% of patients, respectively, met the IRC, while 70% and 55%, respectively, met the SCFRC.ConclusionIn schizophrenia outpatients, a greater proportion of stable cases is detected in remission by SCFRC in comparison with IRC. The SCFRC were more sensitive to the full spectrum of schizophrenia. The SCFRC appear to be valid as a tool and clinically useful as they produce a comprehensive assessment of treatment effectiveness for a wide range of patients.

Symptomatic remission in psychosis and real-life functioning

In 2005 Andreasen proposed criteria for remission in schizophrenia. It is unclear whether these criteria reflect symptom reduction and improved social functioning in daily life. To investigate whether criteria for symptomatic remission reflect symptom reduction and improved functioning in real life, comparing patients meeting remission criteria, patients not meeting these criteria and healthy controls. The Experience Sampling Method (ESM), a structured diary technique, was used to explore real-life symptoms and functioning in 177 patients with (remitted and non-remitted) schizophrenia spectrum disorders and 148 controls. Of 177 patients, 70 met criteria for symptomatic remission. These patients reported significantly fewer positive and negative symptoms and better mood states compared with patients not in remission. Furthermore, patients in remission spent more time in goal-directed activities and had less preference for being alone when they were with others. However, the patient groups did not differ on time spent in social company and doing nothing, and both the remission and non-remission groups had lower scores on functional outcome measures compared with the control group. The study provides an ecological validation for the symptomatic remission criteria, showing that patients who met the criteria reported fewer positive symptoms, better mood states and partial recovery of reward experience compared with those not in remission. However, remission status was not related to functional recovery, suggesting that the current focus on symptomatic remission may reflect an overly restricted goal.

Remission in schizophrenia: results of cross-sectional with 6-month follow-up period and 1-year observational therapeutic studies in an outpatient population

BackgroundA standardized definition of remission criteria in schizophrenia was proposed by the International group of NC Andreasen in 2005 (low symptom threshold for the eight core Positive and Negative Syndrome Scale (PANSS) symptoms for at least 6 consecutive months).MethodsA cross-sectional study of remission rate, using a 6-month follow-up to assess symptomatic stability, was conducted in two healthcare districts (first and second) of an outpatient psychiatric service in Moscow. The key inclusion criteria were outpatients with an International Classification of Diseases, 10th edition (ICD-10) diagnosis of schizophrenia or schizoaffective disorder. Remission was assessed using modern criteria (severity and time criteria), PANSS and Global Assessment of Functioning (GAF). Patients who were stable but did not satisfied the symptomatic criteria were included in a further 1-year observational study, with the first group (first district) receiving risperidone (long-acting, injectable) (RLAI) and the second group (second district) continuing to receiving routine treatment. Symptoms were assessed with PANSS, social functioning with the personal and social performance scale, compliance with rating of medication influences scale, and extrapyramidal side effects with the Simpson-Angus scale.ResultsOnly 64 (31.5%) of 203 outpatients met the criteria for symptomatic remission in the cross-sectional study, but at the end of the 6-month follow-up period, 158 (77.8%) were stable (irrespective of remission status). Among these only 53 (26.1%) patients fulfilled the remission criteria. The observational study had 42 stable patients in the RLAI group and 35 in the routine treatment group: 19.0% in the RLAI group and 5.7% in the control group met remission criteria after 12 months of therapy. Furthermore, reduction of PANSS total and subscale scores, as well as improvement in social functioning, was more significant in the first group.ConclusionsOnly around one-quarter of our outpatient schizophrenic population met full remission criteria. Use of RLAI gave a better remission rate than achieved in standard care with routine treatment. Criteria for remission should take into account clinical course and functioning to support clinical care.

P.3.003 New standardised clinico-functional criteria for therapeutic remission in schizophrenia: description and validation

P.3.003 New standardised clinico-functional criteria for therapeutic remission in schizophrenia: description and validation

Prediction of symptom remission in schizophrenia during inpatient treatment

Objective: Standardized consensus criteria for remission in schizophrenia were recently proposed. The present study applied the symptom-severity component of these criteria to a sample of inpatients in order to determine the rates of remission during inpatient treatment and to explore predictors of remission. Method: A total of 288 inpatients from a multi-centre follow-up programme who fulfilled ICD-10 criteria for schizophrenia were included in the present analyses. PANSS ratings at admission and at discharge from hospitalization were used to examine remission status. Clinical and sociodemographic variables at admission were tested for their ability to predict remission at discharge. Results: In total, 55% of the sample achieved symptom remission during inpatient treatment; 84% percent showed remission with respect to ‘reality distortion’, 85% with respect to ‘disorganization’ and only 65% with respect to ‘negative symptoms’. Logistic regression analysis revealed that the global functioning (GAF) in the year before admission, the total score of the Strauss–Carpenter Prognostic Scale and the PANSS negative subscore at admission were predictive for symptom remission. The regression model showed a predictive value of about 70% and explained 36% of the observed variance. Conclusion: The results highlight the impact of negative symptoms for the course and treatment response of schizophrenic illness.

Association between symptomatic remission and functional outcome in first-episode schizophrenia

Although operational criteria for remission in schizophrenia have recently been proposed, the association of this definition with broader functional outcome has not yet been established in first-episode patients. The severity criteria for remission consist of a score of mild or less on eight core symptoms of schizophrenia. We applied the severity criteria for remission to a sample of patients with first-episode schizophrenia ( n = 76) in order to explore the association with functional outcome five years after first presentation to mental healthcare. We evaluated whether other factors than those included in the remission definition predicted good function in logistic regression models. The discriminatory capacities for remission and other factors for good function were tested using C-statistics. The proportions of remitters and non-remitters having good function were 73% and 17%, respectively. Furthermore, remitters had a higher level of subjective satisfaction with life. In comparison with non-remission, symptomatic remission was strongly associated with good function: odds ratio 13.2, 95% confidence interval, 4.3 to 40.3. A duration of untreated psychosis of three months or less as compared with a longer duration was associated with having good function at a five-year follow-up independently of remission status. The discriminatory capacity for symptomatic remission between having good function vs. not was acceptable ( C-statistic = 0.78), which was significantly improved to an excellent discriminatory capacity by adding duration of untreated psychosis less than three months ( C-statistic = 0.83, p = 0.04). In conclusion, core symptoms of schizophrenia have an important limiting effect on functioning and subjective life satisfaction in the early course of the illness.

Symptom remission in first episode patients

Recently, new remission criteria for schizophrenia has been proposed, based on low symptom severity of core symptoms (the severity criteria), which is sustained over a minimum of 6 months (time criterion). The purpose of this study was to examine, in a secondary analysis, these criteria in a cohort of 240 first episode patients with a mean follow-up of 26.4 months from the Calgary Early Psychosis Program. Eighty-eight subjects (36.7%) met both the severity criteria and time criteria for remission (in-remission group); 47 subjects (19.6%) met only the severity criteria at their most recent assessment (severity only group); 49 (20.4%) subjects had met severity criteria at one or more assessments but did not meet severity or severity and time at the most recent assessment (fluctuating group); and 56 (23.3%) did not meet remission criteria (non-remission group). Those who achieved remission had lower levels of symptoms and higher functioning at baseline and at the final follow-up assessment, improved premorbid functioning, shorter duration of untreated psychosis and increased changes in symptoms over time.

Standardized Remission Criteria in Schizophrenia: Descriptive Validity and Comparability with Previously Used Outcome Measures

Standardized consensus criteria for remission in schizophrenia were recently proposed. As yet, the validity of these criteria and their comparability with previously used outcome measures are unclear. The symptom-severity component of the proposed remission criteria was applied to 288 inpatients who fulfilled the ICD-10 criteria for schizophrenia. Global functioning and psychopathological symptoms were assessed using GAF, PANSS, SANS, HAM-D and CDSS. When patients with symptom remission at discharge from hospitalization (n=158, 54.9%) were compared to those without symptom remission, significant differences were found with respect to the global functioning (GAF) and all observed psychopathological symptom dimensions. The percentage agreement with previously used outcome measures ranged between 52.6 and 80.0%, the kappa values between 0.120 and 0.594. A moderate accordance (kappa value: 0.495) was found with a Clinical Global Impression (CGI) severity score of three or less. The results indicate a high descriptive validity of the symptom-severity component of the proposed remission definition. However, the new criteria differ partially from previously used outcome measures. This aspect should be considered in the interpretation of clinical trials.

Comparative remission rates of schizophrenic patients using various remission criteria

Rationale New standardized criteria for remission in schizophrenia were presented in 2005 which need to be examined in regard to their significance for clinical trials. Objectives and methods Data of six antipsychotic drug trials ( n = 2463) were analyzed by evaluating the proportion of participants who meet the new remission criteria, their symptomatic components, other criteria for remission and simple response-measures (at least 50% Brief Psychiatric Rating Scale (BPRS) reduction and an at least 50% PANSS reduction or a CGI-severity score of “mild or better”). Results: A total of 23.3%/27.2% (last-observation-carried-forward (LOCF)/completer analysis (CO)) of the patients with positive symptoms at baseline met the severity criteria of remission at 4 weeks, 10.5%/20.3% (worst case/CO) met the severity and time criteria at 28 weeks (three studies) and 10.9%/32.4% (worst case/CO) met the severity and time criteria at 52 weeks (one study). At 4 weeks 4.5%/5.5% (LOCF/CO) met the severity criteria when a more stringent severity threshold of “very mild or better” was applied. Absence of symptoms was attained only sporadically. The psychotic symptoms component was met by fewer patients than the negative component. The criteria were more stringent than “at least 50% BPRS reduction” and “CGI-severity score not more than mild” and – for the long-term results – than “at least 50% PANSS reduction”. In the short-term analysis, the criteria were less stringent than “at least 50% PANSS reduction”. Conclusions The applicability of the severity component of the new criteria in clinical trials was confirmed. The time criterion remains difficult to evaluate.

On the concept of remission in schizophrenia

Criteria for remission in schizophrenia have recently been presented. It is unclear how many acutely ill patients meet these criteria and how they compare with previously suggested definitions. We re-analysed seven anti-psychotic drug trials (n = 1,708) of patients with schizophrenia to find out how many met the new remission criteria and their single components, how many met two previously used remission criteria, and how many met simpler measures of response (at least 50% Brief Psychiatric Rating Scale [BPRS] reduction, a Clinical Global Impressions [CGI] improvement score of at least 'much better' or a CGI severity score of 'mild or better'). Thirty-seven percent/41% (last observation carried forward [LOCF]/completer analysis [CO]) of the initially acutely ill patients with positive symptoms met the severity criteria of remission at 4 weeks, and 27%/52% (worst case/CO) met the severity and time criteria at 1 year. Only 13%/21% (LOCF) met the severity criteria at 4 weeks/1 year when an item threshold 'at best very mild symptoms' was applied, and almost no patients were absolutely symptom-free. The psychotic symptoms component was more difficult to achieve than the negative component. The criteria were more stringent than 'at least 50% BPRS reduction' and than 'CGI improvement score of at least much better.' However, the definition 'CGI severity score mild or better' was of a stringency similar to the new remission criteria, which probably explains why fewer patients met previously defined criteria that included this scale. The new remission criteria proved to be an achievable goal for clinical trials. A consensus on the application of their time component is still needed.

Remission criteria for schizophrenia: Evaluation in a large naturalistic cohort

Background Recently, remission criteria for schizophrenia have been proposed, based on low symptom severity of core symptoms (severity criterion), sustained over minimally 6 months (time criterion). Little is known, however, about the added value of the time criterion in addition to the cross-sectional severity criterion. Methods In order to evaluate whether remission is a valid concept for daily clinical practice, the cumulative incidence of patients meeting remission criteria was evaluated in a large naturalistic prospective study of patients with schizophrenia or schizoaffective disorder in different treatment settings in Belgium. The impact of being in remission on global and daily functioning was evaluated. Results Over time, nearly 1 out of 3 patients with a diagnosis of schizophrenia or schizoaffective disorder (29%) met criteria for remission at study endpoint. Patients in remission had better insight in their disorder, a higher level of global functioning and functioned better with respect to daily living tasks, both compared to patients never meeting remission criteria and to patients only meeting the severity criterion but not the time criterion. Of the patients not meeting remission criteria at baseline, 21% attained remission at study endpoint. Conclusion The remission severity and time criteria appear to combine into a valid concept for daily clinical practice and should be a target for treatment.

A remissão em esquizofrenia é possível?

BACKGROUND: The concept of remission is well established in some psychiatric disorders such as depression, but only recently it has been proposed for schizophrenia. OBJECTIVE: The aim of the present paper is to review the new proposed criteria for remission in schizophrenia. METHOD: PubMed search. RESULTS: The concept of remission, response, stability and recover are extensively discussed in the present article, as well as items of the scales used in the definition. CONCLUSION: The concept of remission is characterized by the presence in the last 6 months of symptoms with a maximum threshold severity level (Panss level 3) but which allows a certain degree of social functioning. The dimensions of the concept and respective psychopathological symptoms are: Positive: delusions, hallucinations and unusual thought content. Disorganization: conceptual disorganization and mannerisms and posturing; Negative: blunted affect, passive/apathetic social withdrawal and lack of spontaneity and flow of conversation.

Patient-based and clinician-based support for the remission criteria in schizophrenia.

This analysis characterizes patients with schizophrenia or schizoaffective disorder treated with risperidone who met remission criteria. In a 50-week, open-label trial, stable patients received long-acting injectable risperidone every 2 weeks. Remission criteria included severity (absent-mild ratings on core symptoms of the Positive and Negative Syndrome Scale) and duration (> or =6 months) components. The patients not remitted (severity component only) at baseline (n=394) are the subjects of this report. Measures applied included the PANSS, Clinical Global Impressions-Severity, patient-rated mental health status (Short Form-36), and Drug Attitude Inventory. Among patients who met remission criteria during the study (n=82), mean scores for all 30 PANSS items reflected absent-mild ratings at endpoint. The highest items represented an 'interpersonal' cluster, although mean ratings were still minimal to mild. Remitted patients experienced substantial improvements in Short Form-36 and Drug Attitude Inventory scores at endpoint. Although improvement occurred, it was less robust in patients who remained nonremitted (n=312). Logistic regression analysis found that remission (severity component only) was associated with a 97.1% probability of a 'not ill' rating on the Clinical Global Impressions-Severity. These remission criteria identified patients who differed from the nonremitted population on symptoms of psychopathology, medication attitude, health status, and overall clinical status, supporting the clinical validity of the remission criteria.

Validation of Remission Criteria for Schizophrenia

Remission criteria for schizophrenia have been proposed, consisting of a time criterion and a symptomatic remission criterion. With longitudinal data of a representative patient group (N=317; median follow-up: 1,132 days), validity of the symptomatic remission criterion was investigated. In a group of 145 patients meeting the symptomatic remission criterion at baseline and a group of 172 patients not meeting it at baseline, change over time in remission status was examined in relation to change in various functional outcomes. In both groups, change over time with the symptomatic remission criterion was associated with substantial changes in unmet needs, Global Assessment of Functioning scale scores, satisfaction with services and, to a lesser extent, quality of life. Changing the symptomatic remission criterion to include depression and suicidality did not affect the results. The proposed symptomatic remission criterion has clinical validity and represents the right balance between parsimony and inclusiveness.

Defining remission: proposed criteria and rationale for consensus

New advances in the understanding of schizophrenia etiology, course, and treatment have increased interest on the part of patients, families, advocates, and professionals in the development of consensus-defined standards for clinical status and improvement, including illness remission and recovery. As demonstrated in the area of mood disorders, such standards provide greater clarity around treatment goals, as well as an improved framework for the design and comparison of investigational trials and the subsequent evaluation of interventional effectiveness. Unlike mood disorders, however, the novel application of the concept of standard outcome criteria to schizophrenia must reflect the wide heterogeneity of chronic psychotic illness course and outcome, as well as the variable effects of different treatments on schizophrenia symptomatology. As an initial step in developing operational criteria, an expert Working Group reviewed available definitions and assessment instruments to provide a conceptual framework for symptomatic, functional and cognitive domains in schizophrenia as they relate to remission of illness. The first consensus-based operational criteria for symptomatic remission in schizophrenia is based on distinct thresholds for reaching and maintaining improvement, as opposed to change criteria, allowing for alignment with traditional concepts of remission in both psychiatric and non-psychiatric illness. This innovative approach for standardizing the definition for outcome in schizophrenia also calls for further examination of its validity and utility, as well as the potential for future refinement, particularly in relation to the growing characterization of cognitive dysfunction in psychotic illness. These criteria should facilitate research and support a positive, longer-term approach regarding outcome for patients with schizophrenia. from International Society on Brain and Behaviour: 2nd International Congress on Brain and Behaviour Thessaloniki, Greece. 17–20 November 2005

Standardized remission criteria in schizophrenia

The clinical overview article with this title, by Van Os et al., introduces standardized criteria for remission to a European audience. As the article states, and as implied by the criteria, the time has come to shed pervasive pessimism about the outcome of schizophrenia and to recognize that it is not inevitably a chronic illness that leads to a deteriorating course in all patients. Instead, we must begin to identify subgroups within this heterogeneous disorder that have a differential course and outcome. This concept has been present for many years as ‘the rule of thirds’: one-third improve, one-third deteriorate, and one-third have an intermediate course. But the rule of thirds had no empirical basis. Having criteria for symptomatic remission is the first step that will permit us to base our predictions about course on empirical evidence. The first early studies by Lasser et al. and Van Os et al., not as yet published, confirm that approximately one-third of patients can indeed achieve symptomatic remission based on standard criteria. This type of work is just the beginning. We continue to confront many challenges as we attempt to understand and treat schizophrenia. For example, once we define groups based on outcome, we need to characterize them. What are the best predictors, assessed at the beginning of the illness or intake into a clinical trial, of a good vs. poor outcome? Symptom severity? Specific groups of symptoms, such as negative symptoms? IQ? Other cognitive measures? Premorbid function? Availability of social supports? Treatment received? Treatment side effects? Indicators of drug metabolism, such as cytochrome P450? Neural measures based on structural and/or functional imaging? Any of the genomic measures that are just emerging, such as dysbindin, catechol-o-methyl transferase, or brain derived neurotropic factor? How does improvement or impairment in psychosocial and cognitive function correlate with symptomatic remission? The needs and opportunities are almost endless. The long-term goal of the ‘remission criteria’ initiative is to find better ways to treat people who suffer from schizophrenia. In a more ideal world, and within our reach within the next decade, we will be able use a host of scientific and empirical tools to select the best treatment for an individual patient, based on measures of the type described above. This strategy offers hope rather than pessimism. It bases clinical decisions on evidence rather than guess-work. It replaces a shot-gun approach with a surgical approach to treatment decisions. Defining outcome criteria is the first step necessary to implement this strategy.

Standardized remission criteria in schizophrenia

Recent work has focussed on schizophrenia as a 'deficit' state but little attention has been paid to defining illness plasticity in terms of symptomatic remission. A qualitative review of a recently proposed concept of remission [N.C. Andreasen, W.T. Carpenter Jr, J.M. Kane, R.A. Lasser, S.R. Marder, D.R. Weinberger (2005) Am J Psychiatry 162: 441] is presented. The proposed definition of remission is conceptually viable, and can be easily implemented in clinical trials and clinical practice. Its increasing acceptance may reset expectations of treatment to a higher level, improve documentation of clinical status and facilitate dialogue on treatment expectations. The availability of validated outcome measures based on remission will enhance the conduct and reporting of clinical investigations, and could facilitate the design and interpretation of new studies on cognition and functional outcomes. While useful as a concept, it is important to consider that remission is distinct from recovery. The introduction of standardized remission criteria may offer significant opportunities for clinical practice, health services research and clinical trials.

P.3.040 Remission criteria for schizophrenia evaluated in a large naturalistic cohort

P.3.040 Remission criteria for schizophrenia evaluated in a large naturalistic cohort